Aligned particle based sensor elements

ABSTRACT

The present invention relates to a sensor array for detecting an analyte in a fluid, comprising first and second sensors formed by chemically sensitive resitors, wherein the first sensor comprises a region of aligned conductive material; or where each of the sensors comprises alternating regions of nonconductive regions and aligned conductive regions with each resistor providing an electrical path through both the nonconductive region and the aligned conductive region, while each sensor manifests a different electrical resistance during contact with sample fluids having different analyte concentrations via the monitoring arrangement of having the sensors electrically connected to an electrical measuring apparatus. The aligned conductive particle material is aligned by exposure to either of an electric, magnetic, optical, photo-electric, electromagnetic or mechanical field, which serves to improve signal to noise ratio of vapor sensors allowing Lower Detection Limits for vapors being sensed. Such Lower Detection Limits allow for identification of lower concentrations of hazardous material and is advantageous in medical applications, such as detection of disease states in a patient

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. patent application Ser.No. 09/201,999, filed Dec. 1, 1998, the disclosure of which is herebyincorporated by reference in its entirety for all purposes.

BACKGROUND OF THE INVENTION

[0002] Electronic noses are artificial sensory systems that are able tomimic chemical sensing. In some instances, electronic noses are arraysof sensors, which are able to generate electrical signals in response toanalytes or vapors. For instance, it is possible to detect volatilematerials by directly or indirectly measuring a response, such as aresistance, across each of the sensors in the array. Moreover, byproviding different variables in each sensor of the array, such as thepolymeric make-up of the sensors, it is possible to characterize variouschemical materials according to the response of the array to thatvolatile material.

[0003] The potential applications of electronic noses are great.Examples of applications include, but are not limited to, environmentalcontrol, quality control, assessment of food and beverage products. Forexample, in relation to fish freshness, long chain carbonyl compounds,such as myristaldehyde, can be correlated with fresh fish, whereas shortchain alcohols, dimethylsulfide and amines, which increase as a functionof time, are characteristic of foul smelling fish.

[0004] U.S. Pat. No. 5,571,401, which issued to Lewis et al.(incorporated herein by reference), discloses sensor arrays useful forthe detection of analytes. Each of these sensors comprise a resistorhaving a plurality of alternating nonconductive regions and conductiveregions. As explained therein, gaps exist between the conductive regionsand the nonconductive regions. In these sensors, the electrical pathlength and resistance of a given gap are not constant, but change as thenonconductive region absorbs, adsorbs or imbibes an analyte. The dynamicaggregate resistance provided by these gaps is, in part, a function ofanalyte permeation of the nonconductive regions.

[0005] The foregoing sensor is based on a conductive network in anonconductive matrix. The swelling of the nonconductive matrix causesthe conductive region to move apart changing the resistance of thesensor. The change in the resistance of the sensor can be correlated tothe concentration of the vapor to be detected. The greater theresistance change for a given level of vapor, the lower the detectionlimit of the vapor being identified. It is thus advantageous to maximizethe resistance change associated with the sensor elements.

[0006] One of the major challenges in sensor technology today is toenhance the signal-to-noise ratio (SIN) of a sensor element. Byincreasing the S/N of a sensor element, a lower detection limit ispossible (i.e., the lower the concentration of analyte it is possible todetect). This is particularly useful in applications such as thedetection of low concentrations of explosives, landmine detection or inmedical applications such as in the detection of microorganismoff-gases.

[0007] The response of the sensors upon exposure to vapor is dependenton various factors. One such factor is the percentage of connected pathsthat are broken. The number of connected paths prior to exposure to avapor is related to the percolation threshold. The percolation thresholdis defined as the particle volume fraction at which the conductivity ofthe resistor increases rapidly (i.e., an infinite number of conductivepaths are formed and the lattice essentially transforms from aninsulator to a conductor). At low volume loadings, there are fewconnected paths; whereas at high volume loadings there are manyconnected paths. However, at low volume loadings, there is greatersensor resistance. Unfortunately, there is concomitantly a high degreeof noise at low volume loadings so that the signal to noise ratio isunsatisfactorily low.

[0008] In view of the foregoing, there is a need in the art to improvethe signal to noise of vapor sensors while maintaining low volumeloading. Low volume loading sensors result in more resistance andthereby a broader detection limit and greater dynamic range. The currentinvention fulfills this and other needs.

SUMMARY OF THE INVENTION

[0009] In certain aspects, the present invention provides a sensor arrayfor detecting an analyte in a fluid, comprising: first and secondsensors wherein the first sensor comprises a region of alignedconductive material; and wherein the sensor array is electricallyconnected to an electrical measuring apparatus. Preferably, the firstand second sensors are first and second chemically sensitive resistors,each of the chemically sensitive resistors comprising: a plurality ofalternating regions comprising a nonconductive region, such as anorganic material, and an aligned conductive region. The alignedconductive region comprises an aligned conductive materialcompositionally different from the nonconductive region. Moreover, eachsensor, such as a resistor, provides an electrical path through thenonconductive region and the aligned conductive region; and a firstresponse such as an electrical resistance, when contacted with a firstfluid comprising an analyte at a first concentration, and a secondresponse when contacted with a second fluid comprising the analyte at asecond different concentration.

[0010] In certain embodiments, the conductive region can be alignedusing various processing techniques including, but are not limited to,exposure to an electric field, a thermal field, a magnetic field, anelectromagnetic field, a photoelectric field, a light field, amechanical field or combinations thereof

[0011] Various materials can form the aligned conductive region of thepresent invention. Such materials include, but are not limited to,conductive materials, semi-conductive materials, magnetic materials,photoresponsive materials and combinations thereof The alignedconductive materials are preferably embedded in an organic matrix, suchas a polymeric matrix.

[0012] In another aspect, the present invention relates to a system fordetecting an analyte in a fluid, the system comprising: a sensor arraycomprising first and second sensors wherein the first sensor comprises aregion of aligned conducting material. Preferably, the first and secondsensors are first and second chemically sensitive resistors, eachchemically sensitive resistor comprising a plurality of alternatingregions comprising a nonconductive region and an aligned conductiveregion. Preferably, the aligned conductive region comprises an alignedconductive material compositionally different than the nonconductiveregion. Each sensor, such as a resistor, provides an electrical paththrough the nonconducting region and the aligned conductive region, afirst response such as an electrical resistance, when contacted with afirst fluid comprising an analyte at a first concentration and a seconddifferent response when contacted with a second fluid comprising theanalyte at a second different concentration, wherein the differencebetween the first response and the second response of the firstchemically sensitive resistor being different from the differencebetween the first response and the second response of the secondchemically sensitive resistor under the same conditions; an electricalmeasuring device electrically connected to the sensor array; and acomputer comprising a resident algorithm; wherein the electricalmeasuring device detecting the first and the second responses in each ofthe chemically sensitive resistors and the computer assembling theresponses into a sensor array response profile.

[0013] In yet another aspect, the present invention relates to a methodfor detecting the presence of an analyte in a fluid that can be either aliquid or a gas. The method comprising: providing a sensor arraycomprising first and second sensors, wherein the first sensor comprisesa region of aligned conductive material; and contacting the sensor arraywith the analyte to produce a response thereby detecting the presence ofthe analyte. Preferably, the first and second sensors are first andsecond chemically sensitive resistors, each comprising a plurality ofalternating regions comprising a nonconductive region, such as anorganic material, and an aligned conductive region. The alignedconductive region comprises an aligned conductive materialcompositionally different from the nonconductive region. In this method,each resistor provides an electrical path through the nonconductingregion and the aligned conductive region, a first response such as anelectrical resistance, when contacted with a first fluid comprising ananalyte at a first concentration and a second different response whencontacted with a second fluid comprising the analyte at a seconddifferent concentration.

[0014] These and other features and advantages of the invention will bemore readily apparent and understood when read with the detaileddescription that follows.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015]FIG. 1 shows a graph of a typical resistance versus volume loadingfor a non-aligned composite sensor.

[0016]FIG. 2 shows a graph of resistance versus volume loading for acomposite sensor where the particles have been aligned.

[0017]FIG. 3 shows optical micrographs of unaligned sensor (left) andaligned sensor (right) Black Pearl 2000 (40 wt %) in 1,2-polybutadiene.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS

[0018] Improvement of the signal to noise ratio of vapor sensors allowsfor lower detection limits by increasing the dynamic range. Lowerdetection limits allow for the identification of lower concentration ofmaterials. This is particularly useful when detecting hazardousmaterials or in various medical applications. Surprisingly, it has nowbeen discovered that by intentionally aligning the conductive region,there is an increase in the detection limit, i.e., the sensor is capableof detecting lower concentrations of analyte. As such, the presentinvention provides a sensor array for detecting an analyte in a fluid,comprising: first and second sensors wherein the first sensor comprisesa region of aligned conducting material; and wherein the sensor array isconnected to an electrical measuring apparatus. Preferably, the firstand second sensors are first and second chemically sensitive resistors,each of the chemically sensitive resistors comprising: a plurality ofalternating regions comprising a nonconductive region, such as anonconductive organic material, and aligned conductive region, such asan aligned conductive material or particle. The aligned conductiveregion is compositionally different from the nonconductive region. Thesensors such as resistors, provide an electrical path through thealternating regions comprising a nonconductive region, such as anorganic material, and an aligned conductive region, a first responsewhen contacted with a first fluid comprising an analyte at a firstconcentration, and a second response when contacted with a second fluidcomprising the analyte at a second different concentration.

[0019] As explained previously, the response upon exposure to a vapor isdependent on various factors. One such factor is the percentage ofconnected paths in the alternating regions that are broken. The numberof connected paths prior to exposure to a vapor is related to thepercolation threshold. The percolation threshold is defined as thevolume fraction at which the conductivity of the resistor increasesrapidly. At low volume loadings, there are very few connected paths. Athigh volume loadings, there are many connected paths. Upon exposure tovapors, composite sensors will exhibit a large change in resistance neartheir percolation threshold. Before the advent of the present invention,the noise level associated with such low volume loadings wasprohibitively high. However, by aligning the conductive region, lowervolume loadings can now be used. Moreover, by aligning the conductiveregion, the percolation threshold is easier to obtain at low volumeloadings.

[0020] The sensors of the present invention have an aligned conductiveregion that results in reduced percolation thresholds. Reducedpercolation thresholds mean that a slight swelling of the compositesensor can result is a-very large change in resistance. This is becausethe few conductive particles are all participating in the connectedpaths, and any discontinuity in the connectivity results in a largeresistance change. Thus, the alignment of the conductive region resultsin all of the particles participating in the connected electrical paths.By aligning the conductive region, these systems will produce a stablebase resistance and thereby enhance the signal-to-noise ratio. Toachieve equivalent or near equivalent noise levels, it is important toensure that the alternating regions are stable. This can be accomplishedin the present invention by, for example, cross-linking the polymermatrix in the nonconducting region or by any other suitable means.

[0021] The alignment of the conductive region, e.g., material orparticles, is effected through the application of various processingtechniques. For instance, polarization techniques can be used to alignthe conducting region. Suitable polarization techniques include, but arenot limited to, exposure to an electric field, a thermal field, amagnetic field, an electromagnetic field, a photoelectric field, a lightfield, a mechanical field or combinations thereof The techniquesemployed to align the particles depends in part on the particlecomposition.

[0022] Suitable particles for use in the present invention includeparticles with a permanent magnetic dipole including, but not limitedto, iron, nickel or cobalt require the use of a magnetic field forpolarization to occur. Particles such as carbon black, coke, C₆₀, andthe like, TiO₂, BaTiO₃, In₂O₃, SnO₂, Na_(x)Pt₃O₄, conducting polymers,metals such as platinum, copper, gold, silver etc., polarize withapplication of an electric field. In some embodiments, the conductivematerial is a conducting polymer, or an insulating polymer withconductive fillers. Suitable conductive polymers are disclosed in U.S.Pat. No. 5,571,401, which issued Nov. 5, 1996, and WO 99/31494, whichpublished on Jun. 24, 1999. As disclosed in WO 99/31494, the sensorstaught therein comprise substituted polythiophenes. One polymer is poly(3,3″-dihexyl-2-2″:5′,2″-terthiophene). In a preferred embodiment, theconductive particle is carbon black.

[0023] In an equally preferred embodiment, the conductive material canbe a particle, such as a gold nanoparticle, with a capping ligand shell.A preferred nanoparticle is disclosed in WO 99/27357, entitled“Materials, Method and Apparatus for Detection and Monitoring ChemicalSpecies,” published Jun. 3, 1999. Examples of colloidal nanoparticlesfor use in accordance with the present invention are described in theliterature (see, Templeton et al. J. Am. Chem. Soc. (1 998) 120:1906-1911; Lee et al., Isr. J Chem. (1997) 37: 213-223 (1997);Hostetler et al. LANGMUIR (1998) 14:17-30; Ingram et al., J. Am. Chem.Soc., (1997) 119 :9175-9178; Hostetler et al., J. Am Chem. Soc. (1996)118 :4212-4213; Henglein J Phys. Chem. (1993) 97 :5457-5471; Zeiri, J.Phys. Chem. (1992) 96:5908-5917; Leff et al., LANGMUIR (1996)4723-4730.Moreover, particles such as copper phthalocyanine and phenothiazinepolarize when illuminated. All of these polarization techniques can beused to generate sensors of the present invention.

[0024] Polarization processing, such as magnetic field processing,involves exposure to various polarization mechanisms having differentdirections and optionally, different strengths. For example, duringfabrication of the present sensors, exposure to a magnetic field canoptionally be in one direction, such as in the x-, y- or z-direction; intwo directions, such as x- and y-directions, x-and z-directions or y-and z-directions; or in three directions, such as x-, y- andz-directions. In a preferred embodiment, the polarization processing isalong the same axis as the vapor measurement. For instance, if the vapormeasurement is along the z-direction, particle alignment will be alongthe z-direction. In an equally preferred embodiment, the direction ofexpansion of the alternating regions is along the same axis as the vapormeasurement. As used herein, the x-, y-, and z-axes have theirtraditional meaning, i.e., the x and y axes are in the plane of thesensor substrate and the z axis is perpendicular to the x and y origins.

[0025] In addition to magnetic field processing, sensor fabrication ofthe present invention can include other modes of polarization. Forexample, photosensitive conductive material will be exposed to opticalradiation, such as visible, infrared or ultraviolet light.Electrosensitive conductive material involves exposure to electricfields having different directions and different strengths.

[0026] As previously discussed, enhancing the response of the sensor canbe accomplished by confining the direction of expansion of thealternating regions to be along the axis of measurement or, preferably,along the axis of the particle alignment For instance, a polymer canhave a 2% volume expansion on exposure to a certain vapor concentration.If this swelling can be isolated to one dimension, then the linearexpansion can be as high as 8% causing a much larger change inresistance than would occur without confinement.

[0027] Aligning the conductive region e.g., material or particles, in anonconducting matrix during deposition causes an increase in the numberof conductive paths which in turn, results in a very low baseresistance. As discussed earlier, the formation of a conductive path isrelated to the percolation threshold of the material. The percolationthreshold varies from material to material depending on factors, such asparticle size, shape and composition. Alignment of the conductive regionwill cause percolation to occur at a much lower volume loading. Thus,sensors containing aligned conductive regions will give a larger signalwhen exposed to a vapor compared to a sensor without aligned regions. Asthe nonconductive region, such as an organic polymer, swells, disruptionof the particle chains occurs and a lowering in the conductivity or anincrease in the resistance occurs. As the polymer desorbs, the particlesreturn to their minimum energy state that corresponds to particlealignment.

[0028] Non-sensor alignment of particles are known. For instance, U.S.Pat. No. 4,177,228 issued to Prolss, entitled “Method of Production of aMicro-Porous Membrane for Filtration Plants,” discloses the alignment ofparticles by various techniques. Likewise, U.S. Pat. No. 5,742,223,issued to Simenddinger, entitled “Laminar Non-linear Device withMagnetically Aligned Particles,” discloses composites with magneticallyand electrically conductive particles. In addition, U.S. Pat. No.4,838,347, issued to Dentini, entitled “Thermal Conductor Assembly,”discloses a polymer field with thermally conducting magnetically alignedparticles. Furthermore, U.S. Pat. No. 5,104,210, issued to Tokas,entitled “Light Control Films and Method of Making,” disclosescomposites of magnetically alignable particles.

[0029] In certain aspects, the present invention relates to conductiveregions capable of alignment including, but not limited to, conductive,semi-conductive, magnetic and photoresponsive particles embedded in anonconductive region, such as an organic matrix, For instance, in oneembodiment, particles suitable for use, while preferably spherical, arenot limited by their shape and can even be in the form of flakes.Suitable particulate materials that are magnetic include, but are notlimited to, metals such as, nickel, cobalt and iron and their magneticalloys. Other suitable magnetic particles include, but are not limitedto, oxides and intermetallic compounds as are known in the art.Composite materials can also be used. These material include, but arenot limited to, nickel coated with copper, or magnetically thermallyconducting ceramics (see, U.S. Pat. No. 4,838,347, incorporated hereinby reference). Additional magnetic particles include, but are notlimited to, alloys containing nickel, iron, cobalt and ferrites. Alsoconductive surface coatings can be used. Precious metal coatingsinclude, but are not limited to, silver, gold and precious metal alloys(see, U.S. Pat. Nos. 4,923,739 and 4,737,112 incorporated herein byreference).

[0030] In certain embodiments, the conductive region can be a substrate,such as a particle, coated with metal. Suitable substrates include, butare not limited to, glass, silicon, quartz, ceramic or combinationthereof

[0031] The present invention has advantages over current sensortechnology. One advantage is the use of lower concentrations ofparticles, which leads to ease of dispersion. To a first approximation,the rate of particle sedimentation is proportional to the number ofparticles in the dispersion. Another advantage is the increasedstability of the sensors of the present invention, especially when thepolymer matrix is crosslinked (i.e., the polymer molecules areinterconnected forming a 3-dimensional network). A third advantage is anincrease in the sensitivity of the sensors leading to lower limits ofdetection (i.e., increased dynamic range). The latter advantage is dueto the much higher signal-to-noise ratio given by the sensors having analigned conductive region.

[0032] More particularly, the major advantage of this invention over thesensors of the prior art is that the signal-to-noise ratio is muchhigher. Because of the increase in the signal-to-noise ratio, the limitof detection increases (i.e., a smaller concentration of analyte iscapable of detection). In addition, the response time is faster. Afaster response time is critical in applications such as quality controlwhere the analyte may be on a conveyor belt with a very short time fordetection. In general, sensors with greater response times are betterthan sensor with lower response times. Various sensor responses of thepresent invention include, but are not limited to, resistance,capacitance, inductance, impedance, and combinations thereof.

[0033] In certain aspects, the nonconductive region of the sensorscomprise an organic material. In certain preferred aspects, the organicmaterial is an organic polymer. Organic polymers suitable for use in thepresent invention include, but are not limited to, those set forth inTable 1. TABLE 1 Major Class Examples Main-chain carbon polymerspoly(dienes), poly(alkenes), poly(acrylics), poly(methacrylics),poly(vinyl ethers), poly(vinyl thioethers), poly(vinyl alcohols),poly(vinyl ketones), poly(vinyl halides), poly(vinyl nitriles),poly(vinyl esters), poly(styrenes), poly(arylenes), etc. Main-chainacyclic heteroatom polymers poly(oxides), poly(carbonates),poly(esters), poly(anhydrides), poly(urethanes), poly(sulfonates),poly(siloxanes), poly(sulfides), poly(thioesters), poly(sulfones),poly(sulfonamides), poly(amides), poly(ureas), poly(phosphazenes),poly(silanes), poly(silazanes), etc. Main-chain heterocyclic polymerspoly(furan tetracarboxylic acid diimides), poly(benzoxazoles),poly(oxadiazoles), poly(benzothiazinophenothiazines),poly(benzothiazoles), poly(pyrazinoquinoxalines),poly(pyromellitimides), poly(quinoxalines), poly(benzimidazoles),poly(oxindoles), poly(oxoisoindolines), poly(dioxoisoindolines),poly(triazines), poly(pyridazines), poly(piperazines), poly(pyridines),poly(piperidines), poly(triazoles), poly(pyrazoles), poly(pyrrolidines),poly(carboranes), poly(oxabicyclononanes), poly(dibenzofurans),poly(phthalides), poly(acetals), poly(anhydrides), carbohydrates, etc.

[0034] The sensors of the present invention can be fabricated by manytechniques including, but not limited to, solution casting, suspensioncasting, matrix assisted pulsed laser evaporation (MAPLE), MAPLE-DirectWrite (MAPLE-DW) (see, R. Andrew McGill, et al., IEEE Transactions onUltrasonics, Ferroelectrics, and Frequency Control 45:1370-1380 (1998),and mechanical mixing. In general, solution casting routes areadvantageous because they provide homogeneous structures and are easy toprocess. With solution casting routes, resistor elements can be easilyfabricated by spin, spray or dip coating. Since all elements of theresistor must be soluble, solution casting routes can be somewhatlimited in their applicability. Suspension casting still provides thepossibility of spin, spray or dip coating, but more heterogeneousstructures than with solution casting are expected. With mechanicalmixing, there are no solubility restrictions since it involves only thephysical mixing of the resistor components, but device fabrication ismore difficult since spin, spray and dip coating are no longer possible.In certain embodiments, the resistor is deposited as a surface layer ona solid matrix that provides means for supporting the leads. Typically,the solid matrix is a chemically inert, nonconductive substrate, such asa glass or ceramic.

[0035] Sensor arrays of the present invention are particularlywell-suited to scaled up production by being fabricated using integratedcircuit (IC) design technologies. For example, the chemiresistors caneasily be integrated onto the front end of a simple amplifier interfacedto an A/D converter to efficiently feed the data stream directly into aneural network software or hardware analysis section. Micro-fabricationtechniques can integrate the chemiresistors directly onto a micro-chipthat contains the circuitry for analogue signal conditioning/processingand then data analysis. This provides for the production of millions ofincrementally different sensor elements in a single manufacturing stepusing ink-jet technology. Controlled compositional gradients in thechemiresistor elements of a sensor array can be induced in a methodanalogous to how a color ink-jet printer deposits and mixes multiplecolors. However, in this case, rather than multiple colors, a pluralityof different polymers in a solution which can be deposited are used. Asensor array of a million distinct elements only requires a 1 cm×1 cmsized chip employing lithography at the 10 μm feature level, which iswithin the capacity of conventional commercial processing and depositionmethods. This technology permits the production of sensitive,small-sized, stand-alone chemical sensors,

[0036] The fabrication of the sensors of the present invention involvespolarization processing of the conductive material. Suitablepolarization processing includes, but is not limited to, magnetic fieldprocessing which involves exposure to magnetic fields, photolytic fieldprocessing which involves exposure to optical radiation, electric fieldprocessing which involves exposure to electric fields, and combinationsthereof In photolytic field processing, light sensitive material can beexposed to optical radiation, such as visible, infrared, or ultravioletlight (see, U.S. Pat. No. 4,737,112). All of the foregoing polarizationprocessing techniques can have different axes direction and differentstrengths.

[0037] Preferred sensor arrays have a predetermined inter-sensorvariation in the structure or composition of the nonconductive regions(e.g. the nonconductive organic material). The variation can bequantitative and/or qualitative. For example, the concentration of thenonconductive organic material in the blend can be varied acrosssensors. Alternatively, a variety of different alignment techniques arepossible within the sensor array. For example, the polarizationprocessing techniques (e.g., magnetic and electric fields) can varyacross the array of sensors.

[0038] An electronic nose for detecting an analyte in a fluid isfabricated by electrically coupling the sensor leads of an array ofcompositionally different sensors to an electrical measuring device. Thedevice measures changes in resistivity at each sensor of the array,preferably simultaneously and preferably over time. Frequently, thedevice includes signal processing means and is used in conjunction witha computer and data structure for comparing a given response profile toa structure-response profile database for qualitative and quantitativeanalysis.

[0039] As such, in another embodiment, the present invention, relates toa system for detecting an analyte in a fluid, comprising: a sensor arraycomprising first and second sensors wherein the first sensor comprises aregion of aligned conducting material. Preferably, the first and secondsensors are first and second chemically sensitive resistors, eachchemically sensitive resistor comprising a plurality of alternatingregions comprising a nonconductive region, such as a nonconductiveorganic material, and an aligned conductive region, such as an alignedconductive material compositionally different than the nonconductiveregion. Each resistor provides an electrical path through thealternating nonconducting region and the aligned conductive regions, afirst response such as an electrical resistance, when contacted with afirst fluid comprising an analyte at a first concentration and a seconddifferent response when contacted with a second fluid comprising theanalyte at a second different concentration, the difference between thefirst response and the second response of the first sensor beingdifferent from the difference between the first response and the secondresponse of the second sensor under the same conditions; an electricalmeasuring device electrically connected to the sensor array; and acomputer comprising a resident algorithm; the electrical measuringdevice detecting the first and said second responses in each of thesensors and the computer assembling the responses into a sensor arrayresponse profile.

[0040] Typically, such sensor arrays and electronic noses of the presentinvention comprise at least ten, usually at least 100, and often atleast 1000 different sensors, though with mass deposition fabricationtechniques described herein or otherwise known in the art, arrays of onthe order of at least 10⁶ sensors are readily produced.

[0041] In operation, preferably each resistor provides a firstelectrical resistance between its conductive leads when the resistor iscontacted with a first fluid comprising an analyte at a firstconcentration, and a second electrical resistance between its conductiveleads when the resistor is contacted with a second fluid comprising thesame analyte at a second different concentration. The fluids can beliquid or gaseous in nature. The first and second fluids may reflectsamples from two different environments, a change in the concentrationof an analyte in a fluid sampled at two time points, a sample and anegative control, etc. The sensor array necessarily comprises sensorsthat respond differently to a change in an analyte concentration, i.e.,the difference between the first and second electrical resistance of onesensor is different from the difference between the first and secondelectrical resistance of another sensor. In addition, the sensor arraycan comprise redundant sensors that can be advantageous for maximizingthe signal and thus reducing the noise in the signal.

[0042] In a preferred embodiment, the temporal response of each sensor(resistance as a function of time) is recorded, The temporal response ofeach sensor may be normalized to a maximum percent increase and percentdecrease in resistance which produces a response pattern associated withthe exposure of the analyte. By iterative profiling of known analyses, astructure-function database correlating analyses and response profilesis generated. Unknown analyte can then be characterized or identifiedusing response pattern comparison and recognition algorithms.Accordingly, analyte detection systems comprising sensor arrays, anelectrical measuring device for detecting resistance across eachchemiresistor, a computer, a data structure of sensor array responseprofiles, and a comparison algorithm are provided. In anotherembodiment, the electrical measuring device is an integrated circuitcomprising neural network-based hardware and a digital-analog converter(DAC) multiplexed to each sensor, or a plurality of DACs, each connectedto different sensor(s).

[0043] A wide variety of analytes and fluids may be analyzed by thedisclosed sensors, arrays and noses so long as the subject analyte iscapable of generating a differential response across a plurality ofsensors of the array. Analyte applications include broad ranges ofchemical classes including, but not limited to, organics such asalkanes, alkenes, alkynes, dienes, alicyclic hydrocarbons, arenes,heterocyclics, alcohols, ethers, ketones, aldehydes, carbonyls,carbanions, polynuclear aromatics and derivatives of such organics,e.g., halide derivatives, etc., microorganism off-gases, fungi,bacteria, microbes, viruses, metabolites, biomolecules such as sugars,isoprenes and isoprenoids, fatty acids and derivatives, etc.

[0044] Accordingly, commercial applications of the sensors, arrays andnoses include environmental toxicology and remediation, biomedicine,materials quality control, food and agricultural products monitoring.Further applications include, but are not limited to: heavy industrialmanufacturing (automotive, aircraft, etc.), such as ambient airmonitoring, worker protection, emissions control, and productquality-testing; oil/gas petrochemical applications, such as combustiblegas detection, H₂S monitoring, and hazardous leak detection andidentification; emergency response and law enforcement applications,such as illegal substance detection and identification, arsoninvestigation, hazardous spill identification, enclosed space surveying,and explosives detection; utility and power applications, such asemissions monitoring and transformer fault detection;food/beverage/agriculture applications, such as freshness detection,fruit ripening control, fermentation process monitoring and control,flavor composition and identification, product quality andidentification, and refrigerant and fumigant detection; cosmetic/perfumeapplications, such as fragrance formulation, product quality testing,and patent protection fingerprinting; chemical/plastics/pharmaceuticalsapplications, such as fugitive emission identification, leak detection,solvent recovery effectiveness, perimeter monitoring, and productquality testing; hazardous waste site applications, such as fugitiveemission detection and identification, leak detection andidentification, and perimeter monitoring; transportation applications,such as hazardous spill monitoring, refueling operations, shippingcontainer inspection, and diesel/gasoline/aviation fuel identification;building/residential applications, such as natural gas detection,formaldehyde detection, smoke detection, automatic ventilation control(cooking, smoking, etc.), and air intake monitoring; hospital/medicalapplications, such as anesthesia and sterilization gas detection,infectious disease detection, breath, wound and body fluids analysis,and telesurgey.

[0045] In yet another aspect, the present invention relates to a methodfor detecting the presence of an analyte in a fluid comprising:providing a sensor array comprising first and second sensors, whereinthe first sensor comprises a region of aligned conductive material; andcontacting the sensor array with the analyte to produce a responsethereby detecting the presence of the analyte. Preferably, the first andsecond sensors are first and second chemically sensitive resistors eachcomprising a plurality of alternating nonconductive regions, such asnonconductive organic material, and aligned conductive regions, such asan aligned conductive material compositionally different than thenonconductive region, each resistor providing an electrical path throughthe nonconducting region and aligned conductive region, a first responsesuch as an electrical resistance, when contacted with a first fluidcomprising an analyte at a first concentration and a second differentresponse when contacted with a second fluid comprising the analyte at asecond different concentration.

[0046] The general method for using the disclosed sensor arrays andelectronic noses for detecting the presence of an analyte in a fluidpreferably involves resistively sensing the presence of an analyte in afluid with a chemical sensor comprising first and second conductiveleads electrically coupled to and separated by a chemically sensitiveresistor as described above by measuring a first resistance between theconductive leads when the resistor is contacted with a first fluidcomprising an analyte at a first concentration and a second differentresistance when the resistor is contacted with a second fluid comprisingthe analyte at a second different concentration.

[0047] In certain embodiments, the methods and systems of the presentinvention can be used for monitoring medical conditions and diseaseprocesses. For instance, WO 98/29563, published Jul. 9, 1998, andincorporated herein by reference, discloses a method for monitoringconditions in a patient wherein a sample is obtained from a patient overa period of time. The samples are then flowed over a gas sensor and aresponse is measured. Thereafter, the response is correlated with knownresponses for known conditions. The conditions include, but are notlimited to, the progression and or regression of a disease state,bacterial infections, viral, fungal or parasitic infections, theeffectiveness of a course of treatment and the progress of a healingprocess.

[0048] In another embodiment, the methods and systems of the presentinvention can be used for monitoring medical conditions in a respiringsubject. For instance, WO 98/39470, published Sep. 11, 1998, andincorporated herein by reference, discloses a method for detecting theoccurrence of a condition in a respiring subject. The method comprisesintroducing emitted respiratory gases to a gas sensing device, detectingcertain species present in the gas and correlating the presence of thespecies with certain conditions. A wide variety of conditions can beascertained using this aspect of the present invention. These conditionsinclude, but are not limited to, halitosis, ketosis, yeast infections,gastrointestinal infections, diabetes, alcohol, phenylketonuria,pneumonia, and lung infections. Those of skill in the art will know ofother conditions and diseases amenable to the methods and systems of thepresent invention.

[0049] In certain aspects, the sensor arrays, systems and methods of thepresent invention comprise: first and second sensors wherein the firstsensor comprises a region of aligned conducting material. The secondsensor can also comprise a region of aligned conductive material.However, in certain other embodiments, the second sensor is a differentsensor type. Suitable sensor types include, but are not limited to, asurface acoustic wave (SAW) sensor; a quartz microbalance sensor; aconductive composite; a metal oxide gas sensor, an organic gas sensor;an infrared sensor; a sintered metal oxide sensor; a phthalocyaninesensor; an electrochemical cell; a conducting polymer sensor; acatalytic gas sensor; an organic semiconducting gas sensor; a solidelectrolyte gas sensor; a temperature sensor; a humidity sensor; fiberoptic micromirrors; dye impregnated polymeric coatings on optical fibersand a Langmuir-Blodgett film sensor. Those of skill in the art will knowof other sensors suitable for use in the present invention.

[0050] In certain aspects, the sensors of the present invention comprisea chiral center. For instance, European Patent Application No. 0 794428, published Sep. 10, 1997, describes sensors capable ofdistinguishing between enantiomers. The sensor comprise a pair of spacedapart contacts and a conducting polymer material spanning the gap. Thepolymer has chiral sites in the polymer material formed by incorporatingoptically active counter ions such as camphor sulfonic acid.

[0051] Moreover, WO 99/40423, published Aug. 12, 1999, discloses sensorarrays of that are capable of distinguishing or differentiating betweenchiral compounds. That publication relates to a device for detecting thepresence or absence of an analyte in a fluid, the device comprises asensor, the sensor comprising a chiral region. The sensor comprises aconductive region and a nonconductive region, wherein at least one ofthe conductive and nonconductive regions is chiral, and wherein theanalyte generates a differential response across the sensor.

[0052] In certain other embodiments, the sensor arrays of the presentinvention comprise sensors disclosed in WO 99/00663, published Jan. 7,1999. As taught therein, a combinatorial approach for preparing arraysof chemically sensitive polymer-based sensors are capable of detectingthe presence of a chemical analyte in a fluid contact therewith. Thedescribed methods and devices comprise combining varying ratios of atleast first and second organic materials which, when combined, form apolymer or polymer blend that is capable of absorbing a chemicalanalyte, thereby providing a detectable response. The detectableresponse of the sensors prepared by this method is not linearly relatedto the mole fraction of at least one of the polymer-based components ofthe sensor.

[0053] The following examples are offered by way of illustration and notby way of limitation.

EXAMPLES Example 1

[0054] This Example illustrates the difference in percolation thresholdin non-aligned sensors versus aligned sensors.

[0055] The percolation threshold is defined as the particle volumefraction at which the conductivity of the resistor increases rapidlyi.e., an infinite number of conductive paths are formed and the latticeessentially transforms from an insulator to a conductor. FIG. 1illustrates atypical resistance versus volume loading for a non-alignedcomposite sensor, where the percolation threshold occurs at about 20volume percent filler. FIG. 2 shows a graph of resistance versus volumeloading for a composite sensor where the particles have been aligned.The percolation threshold occurs at about 5 volume percent filler.

Example 2

[0056] This Example illustrates a sensor array that was fabricated bydepositing Black Pearl 2000 (40 wt %) dispersed in 1,2-polybutadiene inthe presence of an electric field.

[0057] The conductive particles respond to the field by migrating tominimum energy states, which in this case corresponds to chain-likestructures aligned parallel to the electric field. As the solventevaporates the chains are locked in place. FIG. 3 illustrates theparticle alignment after using 48 volts across the sensor electrodesduring the deposition process.

[0058] All publications, patents and patent applications mentioned inthis specification are herein incorporated by reference into thespecification in their entirety for all purposes. Although the inventionhas been described with reference to preferred embodiments and examplesthereof, the scope of the present invention is not limited only to thosedescribed embodiments. As will be apparent to persons skilled in theart, modifications and adaptations to the above-described invention canbe made without departing from the spirit and scope of the invention,which is defined and circumscribed by the appended claims.

What is claimed is:
 1. A sensor array for detecting an analyte in afluid, said sensor array comprising: first and second sensors whereinsaid first sensor comprises a region of aligned conductive material; andwherein said sensor array is electrically connected to an electricalmeasuring apparatus.
 2. The sensor array for detecting an analyte in afluid in accordance with claim 1, wherein said first and said secondsensors are first and second chemically sensitive resistors, each of thechemically sensitive resistors comprising: a plurality of alternatingregions comprising a nonconductive region and an aligned conductiveregion that is compositionally different than the nonconductive region,wherein each resistor provides an electrical path through saidnonconductive region and the aligned conductive region; a firstelectrical resistance when contacted with a first fluid comprising ananalyte at a first concentration; and a second electrical resistancewhen contacted with a second fluid comprising said analyte at a seconddifferent concentration.
 3. The sensor array for detecting an analyte ina fluid in accordance with claim 1, wherein said conductive region isaligned by exposure to a member selected from the group consisting of anelectric field, a thermal field, a magnetic field, an electromagneticfield, a photoelectric field, a light field, a mechanical field, andcombinations thereof.
 4. The sensor array for detecting an analyte in afluid in accordance with claim 3, wherein said conductive region iselectrically aligned.
 5. The sensor array for detecting an analyte in afluid in accordance with claim 3, wherein said conductive region ismagnetically aligned.
 6. The sensor array for detecting an analyte in afluid in accordance with claim 3, wherein said conductive region isphotolytically aligned.
 7. The sensor array for detecting an analyte ina fluid in accordance with claim 1, wherein said aligned conductivematerial is a member selected from the group consisting of metal,magnetic alloys, ceramics, oxides, intermetallic compounds, carbonblack, nanoparticles and composite materials.
 8. The sensor array fordetecting an analyte in a fluid in accordance with claim 7, wherein saidconductive material comprises carbon black.
 9. The sensor array fordetecting an analyte in a fluid in accordance with claim 7, wherein saidconductive material comprises a nanoparticle.
 10. The sensor array fordetecting an analyte in a fluid in accordance with claim 7, wherein saidconductive material comprises a metal.
 11. The sensor array fordetecting an analyte in a fluid in accordance with claim 10, whereinsaid metal is a member selected from the group consisting of nickel,cobalt, iron, a ferrite and their magnetic alloys.
 12. The sensor arrayfor detecting an analyte in a fluid in accordance with claim 10, whereinsaid metal is a coating of a substrate, said substrate is a memberselected from group consisting of glass, silicon, quartz, ceramic orcombination thereof.
 13. The sensor array for detecting an analyte in afluid in accordance with claim 10, wherein said metal is a memberselected from the group consisting of a precious metal coating andprecious metal alloys.
 14. The sensor array for detecting an analyte ina fluid in accordance with claim 13, wherein said precious metal coatingis a member selected from the group consisting of silver, gold andplatinum.
 15. The sensor array for detecting an analyte in a fluid inaccordance with claim 7, wherein said conductive region is an oxide. 16.The sensor array for detecting an analyte in a fluid in accordance withclaim 15, wherein said conductive region is a member selected from thegroup consisting of In₂O₃, SnO₂, Na_(x)Pt₃O₄, TiO₂ and BaTiO₃.
 17. Thesensor array for detecting an analyte in a fluid in accordance withclaim 1, wherein said aligned region is a material selected from thegroup consisting of copper phthalocyanine and phenothiazine.
 18. Asystem for detecting an analyte in a fluid, said system comprising: asensor array comprising first and second sensors wherein said firstsensor comprises a region of aligned conductive material which providesa response in the presence of said analyte; an electrical measuringdevice electrically connected to the sensor array; and a computercomprising a resident algorithm; the electrical measuring devicedetecting the response and the computer assembling the response into asensor array response profile.
 19. The system for detecting an analytein a fluid in accordance with claim 18, wherein said first and saidsecond sensors are first and second chemically sensitive resistors, eachchemically sensitive resistor comprising a plurality of alternatingregions comprising a nonconductive region and an aligned conductiveregion that is compositionally different than said nonconductive regionwherein, each resistor provides an electrical path through saidnonconductive region and said aligned conductive region, a firstelectrical resistance when contacted with a first fluid comprising ananalyte at a first concentration and a second different electricalresistance when contacted with a second fluid comprising said analyte ata second different concentration wherein, the difference between saidfirst electrical resistance and said second electrical resistance ofsaid first chemically sensitive resistor being different from thedifference between said first electrical resistance and said secondelectrical resistance of said second chemically sensitive resistor underthe same conditions; and the electrical measuring device detecting thefirst and said second electrical resistances in each of said chemicallysensitive resistors and the computer assembling the resistances into asensor array response profile.
 20. The system for detecting an analytein a fluid in accordance with claim 18, wherein said conductive regionis aligned by exposure to a member selected from the group consisting ofan electric field, a thermal field, a magnetic field, an electromagneticfield, a photoelectric field, a light field or combinations thereof. 21.The system for detecting an analyte in a fluid in accordance with claim20, wherein said conductive region is electrically aligned.
 22. Thesystem for detecting an analyte in a fluid in accordance with claim 20,wherein said conductive region is magnetically aligned.
 23. The systemarray for detecting an analyte in a fluid in accordance with claim 20,wherein said conductive region is photolytically aligned.
 24. A methodfor detecting the presence of an analyte in a fluid, said methodcomprising: providing a sensor array comprising first and secondsensors, wherein said first sensor comprises a region of alignedconductive material; and contacting said sensor array with said analyteto produce a response thereby detecting the presence of the analyte. 25.The method for detecting an analyte in a fluid in accordance with claim24, wherein said first and said second sensors are first and secondchemically sensitive resistors each comprising a plurality ofalternating regions comprising a nonconductive region, and an alignedconductive region that is compositionally different than thenonconductive material, and wherein each resistor provides an electricalpath through said nonconducting regions and aligned conductive regions,a first electrical resistance when contacted with a first fluidcomprising an analyte at a first concentration and a second differentelectrical resistance when contacted with a second fluid comprising saidanalyte at a second different concentration.
 26. The method fordetecting an analyte in a fluid in accordance with claim 24, whereinsaid conductive region is electrically aligned.
 27. The method fordetecting an analyte in a fluid in accordance with claim 24, whereinsaid conductive region is magnetically aligned.
 28. The method fordetecting an analyte in a fluid in accordance with claim 24, whereinsaid conductive region is photolytically or mechanically aligned.